Aging is a risk factor for cognitive impairment from a variety of causes and cognitive impairment is a well-recognized component of age-related neurodegenerative diseases such as Parkinson's disease (PD). While the effects of normal aging on memory have been studied in detail in non-human primates there have been few studies of the effects of age on attention and executive functioning, critical cognitive process for everyday functioning. No studies have examined cognitive status in a non-human primate model of parkinsonism in aged animals. This is important since aging is still the primary risk factor for developing PD and we need to better understand the impact of parkinsonian pathology on a baseline of age-related neurological changes. It is important to know, for example, the extent to which pharmacotherapies (such as nicotinic therapies) that are effective in ameliorating cognitive deficits in younger parkinsonian animals and in normal aged animals remain effective in aged parkinsonian animals with potentially different cognitive and nicotinic receptor profiles. The proposed research has the following specific aims: Specific Aim 1. Examine the effects of age and chronic low dose MPTP exposure on different components of attention and executive functioning (sustained attention, set shifting ability) and working memory (spatial working memory task with different loads on attention and memory) in rhesus macaques as they develop an early stage of parkinsonism; Specific Aim 2. Assess the potential therapeutic effects of sub-type selective nAChR agonists on attention, executive and memory dysfunctions described in Specific Aim 1; Specific Aim 3. Examine normal age-related and early Parkinson-related changes in neurochemistry and autoradiographic distribution of different nAChR subtypes in cortical and subcortical brain regions. The proposed studies will be the first to provide a detailed examination of the scope of the attention, executive function and memory deficits associated with aging and parkinsonism in non-human primates, relate these to alterations in nAChR subtype expression and distribution and test other potential ameliorative therapies. Work resulting from these studies will lead us toward developing improved therapies for age and PD-related cognitive dysfunctions and should help to minimize the effects of aging and PD on cognition, ultimately leading to an improved quality of life in the older population. Aging is a risk factor for cognitive impairment from a variety of causes and cognitive impairment is a well-recognized component of age-related neurodegenerative diseases such as Parkinson's disease (PD). While the effects of normal aging on memory have been studied in detail in non-human primates there have been few studies of the effects of age on other critical cognitive process for everyday functioning such as attention and executive functioning (or on potential therapeutic interventions) and no studies have examined cognitive status in a non-human primate model of parkinsonism in aged animals. Work resulting from the proposed studies will lead us toward developing improved therapies for age and PD-related cognitive dysfunctions and should help to minimize the effects of aging and PD on cognition, ultimately leading to an improved quality of life in the older population.